This application is submitted in response to PAR-07-046 Research on Mind-Body Interactions and Health. We are making application to prospectively examine the cognitive effects of cardiac rehabilitation (CR) in patients with heart failure (HF). Despite advances in treatment, more than 5 million Americans have HF and 500,000 more develop HF each year. Neurocognitive deficits are found in up to 80 percent of HF patients and these deficits are independent predictors of disability and mortality. This risk has been attributed to difficulty adhering to the prescribed medical regimen, which exacerbates HF symptoms. There is reason to believe that participation in CR may improve cognitive function in HF patients. CR provides many benefits to HF patients, including decreased severity of cardiac symptoms, improved functional abilities, and better quality of life. Preliminary work from our lab and others indicates that CR also improves cerebral blood flow and autonomic nervous system (ANS) function, factors that are associated with cognitive function in HF patients. Little is known about the possible cognitive benefits of CR in HF patients. The proposed study will examined cognitive function in 100 HF patients that participate in CR and 100 demographically- and medically-similar HF patients that do not. HF patients will undergo primary assessment at enrollment, 12 week completion of CR, and 12 month follow-up. Primary assessments will include measures of cardiac performance, ANS function, cerebral blood flow, physical function/activity, and cognitive function. Remote assessment of physical activity will also be completed at 6 and 9 month follow-up. Control participants will complete assessments at identical intervals. Finally, a subset of participants (70 in each group) will undergo magnetic resonance imaging at the primary assessments to determine the contribution of structural brain changes to cognitive function. Findings from the proposed study will provide important information regarding: 1) the possible cognitive benefits of CR;2) mechanisms for these benefits;and 3) the relationship between cognitive function and treatment adherence and psychosocial outcomes. Public Health Relevance: Cognitive dysfunction is found in up to 80 percent of heart failure patients and is an independent predictor of disability and mortality. The proposed project will clarify the etiology and reversibility of cognitive dysfunction in persons with heart failure.